THE ROLE OF THE HABENULA-INTERPEDUNCULAR PATHWAY IN MODULATING LEVELSOF CIRCULATING ADRENAL HORMONES

The fasciculus retroflexus (FR) is the major pathway by which the medi al and lateral habenular nuclei project to the interpeduncular nucleus (IPN) and ventral tegmentum. Recent work has suggested that the haben ula-interpeduncular system may be involved in the regulation of states of arousal. Bilateral FR lesions have been shown to disrupt chronical ly, and habenula transplants have been shown to restore normal sleep p atterns in rats [J. Neurosci., 12 (1992) 3282-3290]. In this study, we examined whether FR lesions and habenula cell transplants would also modify chronically the circulating plasma levels of the stress-related hormones, norepinephrine (NE), epinephrine (EPI) and corticosterone. When plasma samples were obtained via retro-orbital eye-bleed during a nesthesia, animals with FR lesions had significantly increased levels of plasma NE, EPI and corticosterone 2-3 months postoperatively compar ed to unoperated controls. Transplants of embryonic habenula cells pla ced near the denervated IPN in FR-lesioned animals restored levels of NE and EPI to normal, but did not attenuate elevated corticosterone le vels. When plasma samples were obtained in conscious animals via indwe lling arterial cannulae, FR-lesioned rats likewise exhibited increased basal levels of corticosterone but plasma levels of catecholamines we re similar to those of unoperated controls. Differences in our results obtained using the two methods of blood sampling may be explained by the effects of anesthesia and stress associated with the eye-bleed met hod. Thus, the effect of FR lesions in increasing plasma levels of cat echolamines may not reflect a difference in basal hormone levels, but a heightened sympathetic adrenomedullary response to stress. While the se results indicate that the integrity of the habenular efferent pathw ay is important in modulating circulating levels of hormones associate d with the stress response, two separate mechanisms appear to control its interactions with sympathetic-adrenal medullary and adrenocortical pathways.